2,003 research outputs found

    Substring filtering for low-cost linked data interfaces

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    Recently, Triple Pattern Fragments (TPFS) were introduced as a low-cost server-side interface when high numbers of clients need to evaluate SPARQL queries. Scalability is achieved by moving part of the query execution to the client, at the cost of elevated query times. Since the TPFS interface purposely does not support complex constructs such as SPARQL filters, queries that use them need to be executed mostly on the client, resulting in long execution times. We therefore investigated the impact of adding a literal substring matching feature to the TPFS interface, with the goal of improving query performance while maintaining low server cost. In this paper, we discuss the client/server setup and compare the performance of SPARQL queries on multiple implementations, including Elastic Search and case-insensitive FM-index. Our evaluations indicate that these improvements allow for faster query execution without significantly increasing the load on the server. Offering the substring feature on TPF servers allows users to obtain faster responses for filter-based SPARQL queries. Furthermore, substring matching can be used to support other filters such as complete regular expressions or range queries

    Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells

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    Hyperinsulinaemia potentially contributes to insulin resistance in metabolic tissues, such as skeletal muscle. The purpose of these experiments was to characterise glucose uptake, insulin signalling and relevant gene expression in primary human skeletal muscle-derived cells (HMDCs), in response to prolonged insulin exposure (PIE) as a model of hyperinsulinaemia-induced insulin resistance. Differentiated HMDCs from healthy human donors were cultured with or without insulin (100 nM) for 3 days followed by an acute insulin stimulation. HMDCs exposed to PIE were characterised by impaired insulin-stimulated glucose uptake, blunted IRS-1 phosphorylation (Tyr612) and Akt (Ser473) phosphorylation in response to an acute insulin stimulation. Glucose transporter 1 (GLUT1), but not GLUT4, mRNA and protein increased following PIE. The mRNA expression of metabolic (PDK4) and inflammatory markers (TNF-α) was reduced by PIE but did not change lipid (SREBP1 and CD36) or mitochondrial (UCP3) markers. These experiments provide further characterisation of the effects of PIE as a model of hyperinsulinaemia-induced insulin resistance in HMDCs

    The scotogenic contact lens: a novel device for treating binocular diplopia

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    Binocular diplopia is a debilitating visual symptom requiring immediate intervention for symptomatic control, whether or not definitive treatment is eventually possible. Where prismatic correction is infeasible, the current standard is occlusion, either by a patch or an opaque contact lens. In eliminating one problem-diplopia-occlusive techniques invariably create another: reduced peripheral vision. Crucially, this is often unnecessary, for the reduced spatial resolution in the periphery limits its contribution to the perception of diplopia. Here, we therefore introduce a novel soft contact lens device that instead creates a monocular central scotoma inversely mirroring the physiological variation in spatial acuity across the monocular visual field, thereby suppressing the diplopia with minimal impact on the periphery. We compared the device against standard eye patching in 12 normal subjects with prism-induced binocular diplopia and 12 patients with binocular diplopia of diverse causes. Indexed by self-reported scores and binocular perimetry, the scotogenic contact lens was comparably effective in eliminating the diplopia while significantly superior in acceptability and its impact on the peripheral visual field. This simple, inexpensive, non-invasive device may thus be an effective new tool in the treatment of a familiar but still troublesome clinical problem

    Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions.

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    Background: Live attenuated SIV induces potent protection against superinfection with virulent virus; however the mechanism of this vaccine effect is poorly understood. Such knowledge is important for the development of clinically acceptable vaccine modalities against HIV. Results: Using a novel, doxycycline dependent, replication-competent live-attenuated SIVmac239Δnef (SIVrtTAΔnef), we show that under replication-permissive conditions SIV-rtTAΔnef is fully viable. Twelve rhesus macaques were infected with a peak plasma vRNA on average two log10 lower than in 6 macaques infected with unconditionally replication-competent SIVΔnef. Consistent with the attenuated phenotype of the viruses the majority of animals displayed low or undetectable levels of viraemia by 42-84 days after infection. Next, comparison of circulating T cells before and after chronic infection with parental SIVΔnef revealed a profound global polarisation toward CD28-CCR7- T-effector memory 2 (TEM2) cells within CD95+CD4+ and CD95+CD8+ populations. Critically, a similar effect was seen in the CD95+ CD4+ population and to somewhat lesser extent in the CD95+ CD8+ population of SIV-rtTAΔnef chronically infected macaques that were maintained on doxycycline, but was not seen in animals from which doxycycline had been withdrawn. The proportions of gut-homing T-central memory (TCM) and TEM defined by the expression of α4β7 and CD95 and differential expression of CD28 were increased in CD4 and CD8 cells under replication competent conditions and gut-homing CD4 TCM were also significantly increased under non-permissive conditions. TEM2 polarisation was seen in the small intestines of animals under replication permissive conditions but the effect was less pronounced than in the circulation. Intracellular cytokine staining of circulating SIV-specific T cells for IL-2, IFN-γ, TNF-α and IL-17 showed that the extent of polyfunctionality in CD4 and CD8 T cells was associated with replication permissivity; however, signature patterns of cytokine combinations were not distinguishable between groups of macaques. Conclusion: Taken together our results show that the global T memory cell compartment is profoundly skewed towards a mature effector phenotype by attenuated SIV. Results with the replication-conditional mutant suggest that maintenance of this effect, that may be important in vaccine design, might require persistence of replicating virus

    Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

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    ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth

    Photonic quantum state transfer between a cold atomic gas and a crystal

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    Interfacing fundamentally different quantum systems is key to build future hybrid quantum networks. Such heterogeneous networks offer superior capabilities compared to their homogeneous counterparts as they merge individual advantages of disparate quantum nodes in a single network architecture. However, only very few investigations on optical hybrid-interconnections have been carried out due to the high fundamental and technological challenges, which involve e.g. wavelength and bandwidth matching of the interfacing photons. Here we report the first optical quantum interconnection between two disparate matter quantum systems with photon storage capabilities. We show that a quantum state can be faithfully transferred between a cold atomic ensemble and a rare-earth doped crystal via a single photon at telecommunication wavelength, using cascaded quantum frequency conversion. We first demonstrate that quantum correlations between a photon and a single collective spin excitation in the cold atomic ensemble can be transferred onto the solid-state system. We also show that single-photon time-bin qubits generated in the cold atomic ensemble can be converted, stored and retrieved from the crystal with a conditional qubit fidelity of more than 85%85\%. Our results open prospects to optically connect quantum nodes with different capabilities and represent an important step towards the realization of large-scale hybrid quantum networks

    Use of an in vitro muscle model to investigate cellular and molecular aspects of exercise physiology: Answering the key questions

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    Research within exercise physiology has traditionally focused upon measurements of gross physiological function of skeletal muscle. However, in order to develop a greater understanding of the exact mechanisms that contribute to skeletal muscle in response to exercise, the cellular and molecular determinants need to be investigated. There is a growing body of in vivo research utilising methods of molecular biology, which has led to the establishment of proposed genes and proteins involved in the adaptation of skeletal muscle to exercise stimuli. In vivo exercise testing poses problems with regards to experimental control; accounting for inter-individual differences and methods relating to tissue sampling are common flaws of such research. In vitro models of skeletal muscle for investigating adaptation to exercise are in their infancy and generally lack biomimicity. It is therefore necessary to develop a model which has greater physiological relevance with respect to exercise, which encompasses the nature of the investigations currently underway in our laboratory
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